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Improved Response of Plaque Psoriasis after Multiple Treatments with Topical 5-Aminolaevulinic Acid Photodynamic Therapy
Abstract
We investigated the clinical response of 10 patients with plaque psoriasis to multiple treatments with photodynamic therapy, using topical application of 5-aminolaevulinic acid followed by exposure to broad-band visible radiation. Treatment was performed up to 3 times per week, with a maximum of 12 treatments, using a light dose of 8 Jcm(-2) delivered at a dose-rate of 15 mW cm(-2). Eight patients showed a clinical response. Out of 19 treated sites, 4 cleared, 10 responded but did not clear and 5 showed no improvement. Of the 4 sites that cleared only 1 did so fully, after 7 treatments, 45 days after the start of therapy. Of the 10 sites that responded partially, the greatest reduction in scale, erythema and induration index occurred after a minimum of 3 and a maximum of 8 treatments. The intensity of 5-aminolaevulinic acid-induced protoporphyrin IX fluorescence, recorded prior to the first treatment, varied between sites on the same patient as well as between patients. There was also a variation in fluorescence intensity recorded from the same site immediately prior to subsequent treatments, although the pretreatment levels generally decreased as the study progressed and then increased as psoriasis relapsed. Biopsies confirmed that fluorescence was localized throughout the epidermis and stratum corneum, but the level was not consistent between sections taken within the same biopsy. We also observed fluorescence at sites distant from the ones that received 5-aminolaevulinic acid, which was not present prior to the start of the treatment programme, but found no evidence of elevated levels of plasma porphyrins. The level of discomfort associated with this therapy increased with increasing values of the calculated photodynamic dose, defined as the product of the initial photosensitizer concentration and the percentage reduction in fluorescence following irradiation. Therefore, although clinical efficacy improved with multiple treatments, unpredictable response and patient discomfort make ALA-PDT unsuitable for the treatment of psoriasis.
... Our systematic search resulted in 765 studies, 23 of them met the inclusion criteria and were included in the systematic review (Fig. 1). Of the 23 studies, 13 evaluated targeted UVB (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), 4 evaluated topical PUVA (20-23), 3 compared topical PUVA vs. targeted UVB (24)(25)(26), and 3 evaluated PDT (27)(28)(29). Six of the included studies were randomized controlled trials (RCTs) and 17 were case series. Of the six RCTs, only three compared the efficacy of targeted UVB phototherapy vs. topical PUVA (24)(25)(26). ...
... Three studies that investigated aminolevulinic acid (ALA)-PDT met the inclusion criteria (27)(28)(29). The pooled efficacy estimate from these studies was 22% (95% CI 10-37%) (Fig. 10). ...
... The main side effect was pain that occurred in 80-100% of the patients, and in 30-38% of them, it was described as intolerable. From these studies, groups treated with high doses (10-30 J/cm 2 ) (27, 28) achieved higher efficacy (33-50%) as compared with groups treated with low doses (5-10 J/cm 2 ) (10-21%) (28,29). ...
Localized phototherapy including topical psoralen plus ultraviolet A (PUVA) and targeted ultraviolet B (UVB), and photodynamic therapy (PDT) have been increasingly used in the treatment of localized psoriasis. Yet, there are no systematic reviews or meta-analyses that scientifically evaluated the pooled efficacy of these treatments in psoriasis. We searched Medline, Embase, and Cochrane databases during the period of January 1980 to June 2012. Our systematic search resulted in 765 studies, 23 of them were included in the review. The primary outcome was 75% reduction in severity score from baseline. A meta-analysis using random effect model found topical PUVA to be more effective than non-laser targeted UVB [odds ratio: 3.48 (95% confidence interval 0.56–21.84), P = 0.183]. The pooled effect estimate of the efficacy (75% reduction in severity score) of topical PUVA, targeted UVB, and PDT were as follows: 77% (topical PUVA), 61% (targeted UVB), and 22% (PDT). Topical PUVA and targeted UVB phototherapy are very effective in the treatment of localized psoriasis. Topical PUVA seems more effective than non-laser targeted UVB phototherapy. On the other hand, PDT has low efficacy and high percentage of side effects in treating localized psoriasis.
... Ce qui est appuyé par le fait qu'in vitro les cellules de rate des souris MRL/1rp activées par l'adjuvant sont plus sensibles à la PDT que les cellules de rate non activées à cause d'une accumulation élevée de PS [180]. [183]. Récemment une étude a révélé que cette hétérogénéité de réponse en fonction des sites traités était corrélée à l'épaisseur de la couche cornée (startum corneum) correspondant à la couche la plus externe de la peau [184]. ...
... Et pour cette raison la lumière rouge semble plus appropriée que la lumière bleu ou verte. Cependant l'utilisation de la PDT dans le traitement du psoriasis reste limitée en raison de la forte douleur ressentie par les patients au cours du traitement [183,186]. Mais bien avant ces deux études, différentes études cliniques montraient des résultats prometteurs quant à l'utilisation de la photochémothérapie extracorporelle (PUVA thérapie) dans le traitement de patients atteints de MC [190][191][192]. Une étude pilote de Reinisch et al, sur 10 patients stéroides dépendants atteints de MC, démontra une bonne efficacité de la photochémothérapie extracorporelle. ...
Les maladies inflammatoires chroniques de l’intestin (MICI) sont des pathologies incurables et de surcroit associées à un risque élevé de cancer colorectal (CCR). Les thérapies actuellement disponibles pour le traitement des MICI et la prévention du CCR associé, sont loin d’être optimales. Récemment la thérapie photodynamique (PDT) utilisant de faibles doses de photosensibilisateur et/ou de lumière, appelée alors LDPDT (Low dose-PDT), est apparue comme une nouvelle modalité de traitement pour des pathologies inflammatoires telles que le psoriasis ou l’arthrite rhumatoïde. Dans cette étude, nous avons évalué sur modèles murins l’effet thérapeutique de la LDPDT à l’aide d’une formulation liposomale de mTHPC (méta-tetra-hydroxyphenylchlorine, connu sous le nom de Foslip®), dans le traitement des MICI et la prévention du CCR. Des analyses endoscopiques, macroscopiques et histologiques ont été réalisées et le taux de myéloperoxidase (MPO) au sein de la muqueuse colique a été quantifié par test ELISA. L’expression des cytokines a été quantifiée par RT-PCR, la perméabilité de la barrière intestinale a été évaluée par immuno-marquage et une analyse du microbiote intestinal a été effectuée par pyrosequençage. La LDPDT-Foslip® a significativement réduit la sévérité de la colite en supprimant l’inflammation intestinale notamment par diminution des cytokines pro-inflammatoires et suppression de l’infiltration par les neutrophiles. Elle a également permis de corriger la perméabilité de la barrière intestinale. De plus, la LDPDT-Foslip® a clairement démontré un effet préventif sur le développement du cancer colorectal en supprimant l’inflammation chronique et en corrigeant la dysbiose. En conséquence, la LDPDT-Foslip® pourrait être considérée comme une nouvelle modalité de traitement pour supprimer l’inflammation intestinale et prévenir le développement du cancer colorectal chez les patients atteints de MICI.
... ALA has the advantage of a having a short half-life, reducing the risk of prolonged systemic photosensitivity [47]. Short topical contact, i.e., 30 min to 2 h, of ALA-PDT has proved to be a safe and effective treatment for a variety of dermatological disorders including psoriasis [146][147][148][149]. A series of treatments is usually necessary with variable clinical response. ...
... Robinson et al. [147] performed a study on 10 patients with chronic plaque psoriasis using multiple treatment exposures. All patients received topical 20% ALA with broad-band visible radiation and a dose of 8 J/cm 2 at 15 m/W/cm 2 . ...
Photodynamic therapy (PDT) is an intensively studied part of medicine based on free radicals. These reactive species, extremely harmful for whole human organism, are used for eradication numerous diseases. Specific structure of ill tissues causes accumulation free radicals inside them without attack remaining healthy tissues. A rapid development of medicine and scientific research has led to extension of PDT towards treatment many diseases such as cancer, herpes, acne and based on antimicrobials. The presented review article is focused on the aforementioned disorders with accurate analysis of the newest available scientific achievements. The discussed cases explicitly indicate on high efficacy of the therapy. In most cases, free radicals turned out to be solution of many afflictions. Photodynamic therapy can be considered as promising treatment with comparable effectiveness but without side effects characteristic for chemotherapy.
... Ce qui est appuyé par le fait qu'in vitro les cellules de rate des souris MRL/1rp activées par l'adjuvant sont plus sensibles à la PDT que les cellules de rate non activées à cause d'une accumulation élevée de PS [180]. [183]. Récemment une étude a révélé que cette hétérogénéité de réponse en fonction des sites traités était corrélée à l'épaisseur de la couche cornée (startum corneum) correspondant à la couche la plus externe de la peau [184]. ...
... Et pour cette raison la lumière rouge semble plus appropriée que la lumière bleu ou verte. Cependant l'utilisation de la PDT dans le traitement du psoriasis reste limitée en raison de la forte douleur ressentie par les patients au cours du traitement [183,186]. Mais bien avant ces deux études, différentes études cliniques montraient des résultats prometteurs quant à l'utilisation de la photochémothérapie extracorporelle (PUVA thérapie) dans le traitement de patients atteints de MC [190][191][192]. Une étude pilote de Reinisch et al, sur 10 patients stéroides dépendants atteints de MC, démontra une bonne efficacité de la photochémothérapie extracorporelle. ...
Inflammatory bowel diseases (IBD) are chronic, incurable diseases associated with a high risk of colorectal cancer. Currently available therapies for the treatment of IBD and CRC prevention are far from optimal. Recently, photodynamic therapy (PDT) using low doses of photosensitizer and/or light, called LDPDT (Low-dose PDT) has emerged as a new treatment modality for inflammatory diseases such as psoriasis or rheumatoid arthritis.In this study, we assessed the therapeutic effect of LDPDT using a liposomal formulation of mTHPC (meta-tetra-hydroxyphenylchlorin, called Foslip®) in the mouse model for the treatment of IBD and prevention of CRC.Endoscopic, macroscopic and histological analyzes were performed and the rate of myeloperoxidase (MPO) in the colonic mucosa was quantified by ELISA. Cytokine expressions were quantified by RT-PCR, the permeability of the intestinal barrier was evaluated by immunolabeling and intestinal microbiota analysis was done by pyrosequencing. LDPDT-Foslip® significantly reduced colitis severity by suppressing intestinal inflammation including reduction of proinflammatory cytokines and suppression of neutrophil influx. Moreover, LDPDT restores the integrity of the intestinal barrier. In addition, LDPDT-Foslip® has clearly demonstrated a preventive effect on colorectal cancer development by suppressing chronic inflammation and changing the composition of intestinal microbiota. Accordingly, LDPDT-Foslip® could be considered as a new treatment modality to abrogate intestinal inflammation and prevent the development of colorectal cancer in patients with IBD.
... Its susceptibility to PDT with red light has been previously studied. [5][6][7][8][9][10] PpIX is also present in psoriatic skin without the preceding application of its precursor, because of endogenous levels of PpIX. 11 Consequently, the interaction of blue light and endogenous photosensitizers, like PpIX, in psoriasis may represent a new principle for photodynamic treatment of psoriasis without the application of an exogenous photosensitizer. ...
... 15,16 Improvement of psoriasis plaque severity after ALA-PDT has been shown in different studies. 7,8,10 Increased PpIX levels have also been demonstrated in psoriasis plaques without the administration of ALA. Endogenous PpIX is mainly present in the stratum corneum of patients with psoriasis. ...
Background:
Protoporphyrin IX is present in psoriatic skin without the preceding application of aminolevulinic acid. Therefore, endogenous photosensitizers in psoriasis are a potential target for photodynamic treatment with high-dose visible light.
Objectives:
In the present pilot study, treatment with high-dose blue and red light in psoriasis were analysed with respect to clinical improvement and potential side-effects.
Methods:
In 20 patients, two stable psoriatic plaques were treated with either blue or red light, three times weekly for four consecutive weeks. To remove scaling that could potentially interfere with penetration of the light into the skin, daily application of 10% salicylic acid in petrolatum was started at the screening visit and continued until the end of the study.
Results:
Clinical improvement was seen after treatment with blue as well as after treatment with red light. With respect to scaling and induration, no major differences between both light sources were seen. Improvement of erythema, however, continued in blue light irradiated plaques throughout the whole study period, whereas after red light no significant improvement was seen after six illuminations.
Conclusions:
The clinical improvement of psoriasis, with respect to erythema, in particular after blue light and to a lesser extent after red light indicates that visible light treatment could represent a treatment option for psoriasis.
... This therapy is effective in the treatment of AK, Bowen's disease and superficial BCC, but insufficiently effective in treating nodular BCC and squamous cell carcinoma (SCC) (4)(5)(6)(7). There are some reports in the literature about the trials of TPT in the treatment of viral warts, acne, psoriasis and cutaneous T-cell lymphoma (8)(9)(10)(11)(12)(13)(14)(15)(16). This therapy has shown numerous advantages regarding the number, location and size of lesions, multiple treatments, outpatient conditions and cosmetic results (17). ...
... It seems that ALA-TPT in patients with vulgar psoriasis (VP), when administrated 3 times per week gives results comparable with dithranol (13). Multiple-session treatment had better but non-predictable results, limited mostly by pain (15,60). Based on clinical and experimental data available, TPT shows distinct antipsoriatic potential. ...
Topical photodynamic therapy is a therapeutic modality in development, thus arises grate interest among dermatologists worldwide. It is an effective therapy for actinic keratosis, superficial BCC and Bowenos disease. Treatment efficacy, good cosmetics, low risk of skin cancer, low invasiveness, low rate of adverse events, facility for treating multiple or large lesions, especially in poor healing sites and, for penile, digital and facial involvement, low general toxicity and possibility of repeating the treatments with the same efficiency, enable topical photodynamic therapy to become increasingly practiced treatment modality. Researching aimed topical photodynamic therapy to prove as a treatment modality for clinical use in other dermatoses, is in experimental phase. To answer the question when dermatologist should consider using topical photodynamic therapy treatment modatility, we are present available date.
... Indeed, immunohistochemical investigations of psoriatic lesions treated with PDT showed normalization of epidermal proliferation and differentiation, decreased infiltration of pathogenetically relevant T-cell subsets [59], and reduced dermal neovascularization [60]. However, clinical results have been disappointing with limited and unpredictable clinical response and significant pain, stinging, and burning during and after irradiation is frequent [60][61][62][63][64]. In addition, costs could most often be excessive because psoriatic lesions may cover a large part of the body surface and clearing of lesions, if any, is seen after repeated treatments. ...
Background:
In the past 30 years, topical photodynamic therapy (PDT) has been investigated for the treatment of a broad spectrum of cosmetic, inflammatory, and infectious skin conditions with variable, and often contrasting, results. However, the non-expert clinician may be in difficulty evaluating these results because different sensitizers, concentrations, formulations, light sources, and irradiation protocols have been used. In addition, many of these studies have poor quality design being case reports and uncontrolled studies of few cases.
Summary:
With the aim to clarify the potential usefulness of PDT for the treatment of infectious and inflammatory skin diseases as well as selected cosmetic indications, we searched for randomized controlled clinical trials, non-randomized comparative studies, retrospective studies, and case series studies with a number of at least 10 patients, published since 1990. Later, we reappraised the results in order to give a simple critical overview. Key Messages: Evidence from the literature seems to strongly support the use of ALA- and MAL-PDT for the treatment of common skin diseases such as acne, warts, condylomata, and Leishmania skin infection and for photorejuvenation, i.e., the correction of selected cosmetic changes of aging and photoaging. For other disorders, the level of evidence and strength of recommendation are lower, and controlled randomized studies with prolonged follow-ups are necessary in order to assess the clinical usefulness and other potential advantages over current treatment options.
... The other advantage is that repeated photosensitization of bacterial cells does not induce a selection of resistant strains. 10 Although PACT is gaining increasing acceptance for the treatment of locally occurring infections such as psoriasis 11 and scleroderma 12 in dermatology, it is not, at present, a mainstream therapeutic option. ...
Photodynamic antimicrobial chemotherapy (PACT) is an effective method for killing bacterial cells in view of the increasing problem of multiantibiotic resistance. We herein reported the PACT effect on bacteria involved in skin infections using a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5). Compared with its anionic ZnPc counterpart, ZnPc-(Lys)5 showed an enhanced antibacterial efficacy in vitro and in an animal model of localized infection. Meanwhile, ZnPc-(Lys)5 was observed to significantly reduce the wound skin blood flow during wound healing, indicating an anti-inflammation activity. This study provides new insight on the mechanisms of PACT in bacterial skin infection. © 2016 Society of Photo-Optical Instrumentation Engineers (SPIE).
... In other words, PACT is based on an initial photosensitization of the skin, followed by irradiation with visible light producing cytotoxic singlet oxygen. As a low-cost approach for the treatment of locally occurring infection, PACT was reported to be used for the treatment of diseases such as psoriasis (Robinson et al., 1999) and scleroderma (Karrer et al., 2000) in dermatology. ...
Folliculitis, furunculosis and acne vulgaris are very common skin disorders of the hair follicles and are associated with large grease-producing (sebaceous) glands. Although the detailed mechanisms involved these skin disorders are not fully understood, it is believed that the bacteria Propionibacterium acnes and Staphylococcus aureus are the key pathogenic factors involved. Conventional treatments targeting the pathogenic factors include a variety of topical and oral medications such as antibiotics. The wide use of antibiotics leads to bacterial resistance, and hence there is a need for new alternatives in above bacterial skin treatment. Photodynamic antimicrobial chemotherapy (PACT) is based on an initial photosensitization of the infected area, followed by irradiation with visible light, producing singlet oxygen which is cytotoxic to bacteria. Herein we reported a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5) and its PACT effect for the bacteria involved in these skin infections. Our results demonstrated strong bactericidal effects of this photosensitizer on both strains of the bacteria, suggesting ZnPc-(Lys)5 as a promising antimicrobial photosensitizer for the treatment of infectious diseases caused by these bacteria
... Photodynamic therapy (PDT) represents another potential and effective modality for the treatment of superficial skin growths, especially AKs, Bowen disease, superficial BCC, and chronic inflammatory diseases such as psoriasis. 19,20,21,22,23,24,25,26 At present, topical ALA and MAL are the most promising PDT agents for many dermatologic uses. ...
... Ιn vitro, PDT has been shown to have a significant influence on the balance of collagen synthesis [11] and fibroblast proliferation [12]. In addition ALA-PDT has been shown to have significant effects on the local vasculature [13] and leads to the induction of local immunological responses that are dependent on the illumination scheme [14,15]. ...
Background
The aesthetic result after brachytherapy, especially hypopigmentation, remains a significant problem. Given that brachytherapy may be carcinogenic, it is difficult to recommend this treatment in young patients. For these reasons, there is a need for alternatives to radiation.
Methods
The purpose of this study was to evaluate the effectiveness of adjuvant photodynamic therapy (PDT) using aminolevulinic acid after keloid excision and to compare it to keloid excision followed by brachytherapy. To assess outcome, the Patient and Observer Scar Assessment Scale (POSAS) was used.
Results
Thirty-four patients treated for 45 keloids were evaluated. Twenty-two patients (27 lesions) received brachytherapy and 12 (18 lesions) received PDT. The observers scored a mean POSAS of 19.1 (range 13.0–34.0) for brachytherapy and 24.6 (range 11.0–37.0) for PDT (p = 0.005). The independent observers scored a mean POSAS of 14.6 (range 10.0–20.0) for brachytherapy and 18.6 (range 9.0–42.0) for PDT (p = 0.018). The patients reported a significantly better mean POSAS score after brachytherapy (22.8, range 7.0–53.0) than following PDT (34.2, range 11.0–63.0). The patients’ POSAS score showed no significant difference for the item “general impression” for both treatment groups; the observers scored significantly higher for PDT treatment. The independent observers revealed a higher score for general impression after PDT although not reaching significance.
Conclusions
Patients and observers appear to be more satisfied with the results after brachytherapy than PDT. However, patients still have a positive general impression after PDT. Adjunctive aminolevulinic acid–PDT for the treatment of keloids could be used as an alternative for brachytherapy.
Level of Evidence: Level IV, therapeutic study.
... Då metoden även anses ha immunmodulerande effekter som liknar PUVA (143), har den också prövats på psoriasis. I några mindre studier (4-21 patienter) har man funnit mer (144,145) eller mindre (146,147) god klinisk respons, men framför allt är biverkningar i form av smärta kraftigt begränsande. Metoden rekommenderas inte för behandling av psoriasis i Guidelines från British Photodermatology Group (148). ...
... ALA-PDT has none of these problems. Attempts to treat psoriasis with systemic and topical photodynamic therapy have been reported previously, but yielded only marginal results in terms of efficacy and patient tolerability (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). The tolerability issue refers to severe pain experienced during PDT illumination of the psoriatic plaques (44). ...
We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis.
... It is unclear whether the disease itself is a determinant of PDTinduced pain as most of the studies reported have been in skin cancers. However, the published use of PDT in the treatment of viral warts (31,32), psoriasis (33,34) and acne (35,36) suggests that treatment of these conditions is associated with more pain. This is of interest as, for non-tumour indications, such as acne and psoriasis, lower light doses and less intensive PDT regimes have generally been used. ...
Topical photodynamic therapy (PDT) is increasingly used in dermatology, particularly for the treatment of superficial non-melanoma skin cancer and dysplasia. Treatment is generally considered to be well tolerated, although pain during PDT can be a limiting factor. This review explores the adverse effects of topical PDT.
A thorough search of the literature using Medline was undertaken and published data were evaluated and presented in conjunction with our own experience.
Pain during PDT is the most commonly reported adverse effect and may prevent successful treatment delivery, although low-irradiance regimes and use of nerve blocks or cooling air can be used to reduce pain. Other acute and chronic adverse effects are reported but do not seem to be limiting factors in the use of topical PDT. To date, there is no convincing evidence for a carcinogenic effect of this treatment.
Topical PDT is associated with few significant adverse effects, although methods to optimize regimes and minimize pain are required to improve the acceptability of this therapy for patients.
Cancer therapy, especially for tumors near sensitive areas, demands precise treatment. This review explores photodynamic therapy (PDT), a method leveraging photosensitizers (PS), specific wavelength light, and oxygen to target cancer effectively. Recent advancements affirm PDT’s efficacy, utilizing ROS generation to induce cancer cell death. With a history spanning over decades, PDT’s dynamic evolution has expanded its application across dermatology, oncology, and dentistry. This review aims to dissect PDT’s principles, from its inception to contemporary medical applications, highlighting its role in modern cancer treatment strategies.
Photodynamic therapy (PDT) in the treatment of psoriasis remains the subject of much debate. There is no consensus in the scientific community about effective and safe PDT regimens for psoriasis. Described in the published materials doses and concentrations of photosensitizers for psoriasis, as well as light doses, differ by dozens of times. The purpose of this review is to analyze the efficacy and safety profile of various PDT regimens for psoriasis. Some studies demonstrate 100% effectiveness of the method in certain modes (complete or partial clearance of psoriasis foci after PDT). In particular, such efficiency was obtained with the application of 20% 5-ALA (light dose 15 J/cm2) and 0.1% methylene blue (light dose 15 J/ cm2). The main factor limiting the use of PDT in psoriasis, and in some cases even being the reason for treatment interruption, is severe pain during the irradiation procedure. This requires careful development of PDT regimens in patients with psoriasis.
Psoriasis (PS) is an immune-mediated skin disease with substantial negative effects onpatient quality of life. Despite significant progress in the development of novel treatment options overthe past few decades, a high percentage of patients with psoriasis remain undertreated and requirenew medications with superior long-term efficacy and safety. One of the most promising treatmentoptions against psoriatic lesions is a form of phototherapy known as photodynamic therapy (PDT),which involves either the systemic or local application of a cell-targeting photosensitizing compound,followed by selective illumination of the lesion with visible light. However, the effectiveness ofclinically incorporated photosensitizers in psoriasis treatment is limited, and adverse effects such aspain or burning sensations are frequently reported. In this study, we performed a literature reviewand attempted to provide a pooled estimate of the efficacy and short-term safety of targeted PDT inthe treatment of psoriasis. Despite some encouraging results, PDT remains clinically underutilized.This highlights the need for further studies that will aim to evaluate the efficacy of a wider spectrumof photosensitizers and the potential of nanotechnology in psoriasis treatment.
b>Hintergrund: In den letzten 30 Jahren wurde die topische photodynamische Therapie (PDT) zur Behandlung eines breiten Spektrums von kosmetischen, entzündlichen und infektiösen Hauterkrankungen mit variablen und oft kontrastierenden Ergebnissen untersucht. Allerdings kann es für den nicht fachkundigen Arzt schwierig sein, diese Ergebnisse zu bewerten, da verschiedene empfindlichkeitssteigernde Stoffe, Konzentrationen, Formulierungen, Lichtquellen und Bestrahlungsprotokolle verwendet wurden. Darüber hinaus haben viele dieser Studien als Fallberichte und unkontrollierte Studien von wenigen Fällen eine schlechte Design-Qualität. Zusammenfassung: Mit dem Ziel, den potenziellen Nutzen von PDT für die Behandlung von infektiösen und entzündlichen Hauterkrankungen sowie ausgewählten kosmetischen Indikationen zu klären, suchten wir nach randomisierten kontrollierten klinischen Studien, nicht randomisierten Vergleichsstudien, retrospektiven Studien und Fallreihenstudien mit einer Anzahl von mindestens 10 Patienten, die seit 1990 veröffentlicht wurden. Später haben wir die Ergebnisse neu bewertet, um einen einfachen kritischen Überblick zu geben. Die Kernbotschaften: Literaturbelege scheinen die Verwendung von ALA- und MAL-PDT zur Behandlung von häufigen Hauterkrankungen wie Akne, Warzen, Kondylomen und Leishmania-Hautinfektionen sowie zur Photorejuvenation, d. h. zur kosmetischen Korrektur ausgewählter kosmetischer Alterungs- und Lichtalterungsschäden stark zu unterstützen. Für andere Erkrankungen sind die Evidenz und die Stärke der Empfehlung niedriger, und kontrollierte randomisierte Studien mit verlängerten Nachbeobachtungen sind notwendig, um den klinischen Nutzen und andere potenzielle Vorteile gegenüber den aktuellen Behandlungsoptionen zu beurteilen.
Psoriasis is an immune-mediated, chronic and recurrent inflammatory skin disease, prevalent worldwide, and represents an important burden in life quality of patients. The most common clinical variant is termed as psoriasis vulgaris or plaque psoriasis, which with an individualized and carefully monitored therapy can decrease the patients’ morbidity and improving their life quality. The aim is to achieve disease control, minimize the adverse drug effects, and tailor the treatment to individual patient factors. Photodynamic therapy (PDT) is based on local or systemic administration of a non-toxic photosensitizer followed by irradiation with a particular wavelength to generate reactive oxygen species (ROS), mainly highly cytotoxic singlet oxygen (1O2). The generation of these species results in the attack to substrates involved in biological cycles causing necrosis and apoptosis of affected tissues. Photosensitizers are found in natural products and also obtained by partial syntheses from abundant natural starting compounds. They can be isolated at low cost and in large amounts from plants or algae. Therefore, this manuscript reviews the use of molecules from vegetal sources as photosensitizer agents for the PDT of psoriasis. Psoriasis pathogenesis, management and treatment were reviewed. PDT principles, fundamentals and utilization for the treatment of psoriasis were also discussed. Photosensitizers for PDT of psoriasis are also reviewed focusing on those from vegetal sources. Despite the PDT is utilized for the treatment of psoriasis, very little amount of photosensitizers from plant sources are utilized, such as chlorophyll derivatives and hypericin; however, other natural photosensitizers such as curcumin, could also be investigated. They could constitute a very important, safe and cheap alternative for the successful photodynamic treatment of psoriasis.
Introduction: Photodynamic therapy (PDT) involves the application of a topical photosensitizer, irradiation with light, and oxygen to produce cytotoxic reactive oxygen species that selectively destroy damaged cells while leaving normal skin intact. Topical PDT is a commonly used treatment for non-melanoma skin cancers (NMSCs) due to its excellent clearance rate and cosmetic outcomes. However, PDT is emerging as an off-label treatment modality for many dermatological conditions.
Methods: A literature review using MEDLINE was performed to identify randomized controlled trials conducted for currently approved and off-label clinical indications and photosensitizers for PDT between 2012 and 2018.
Results: The photosensitizer indole-3 acetic acid reduces the incubation time (<30 minutes), avoids the need for photoprotection after irradiation, and inflicts minimal pain. Cyclic PDT in individuals with evidence of field cancerization delays the mean time of actinic keratosis appearance and reduces the total number of new actinic keratoses. Substantial evidence exists outlining the utility of PDT in photorejuvenation due to its ability to improve skin texture, wrinkles, and firmness. The addition of microdermabrasion, microneedling, curettage, or various lasers improves clinical efficacy and cosmetic outcomes.
Discussion: PDT applications are expanding rapidly. Clinicians must stay up to date regarding the efficacy and safety of PDT applications.
Topical photodynamic therapy (PDT) is widely used to effectively treat superficial non‐melanoma skin cancer and dysplasia. As with any therapeutic approach, the risk/benefit profile must be taken into account on an individual patient basis; in general, PDT is well tolerated. Historically, PDT‐induced pain has been a potentially limiting factor, but with optimisation of treatment parameters, such as the introduction of lower irradiance regimens, pain is now uncommonly a major issue. Expected “adverse” effects of a phototoxic insult also include inflammation, manifest as erythema, exudation and sometimes urticaria. Other side‐effects are uncommon and include scarring, altered hair growth or pigmentary change and allergic reactions. The theoretical risk of carcinogenesis with cumulative PDT treatments is unproven and indeed PDT can be considered as a prophylactic approach in high‐risk patients, such as the immunosuppressed. This review summarises the current evidence relating to the adverse effects of topical PDT as part of the guideline updating project on this subject¹ and attempts to interpret this evidence in the context of patient risk (Table 1).
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Die photodynamische Therapie (PDT) stellt eine effektive Behandlungsform für ausgewählte dermatologische Erkrankungen dar. Die fehlende Invasivität der topischen PDT mit 5-Aminolävulinsäure (ALA) oder ihrem Methylesterderivat, die guten kosmetischen Ergebnisse sowie die bisher fehlenden Hinweise auf eine potenzielle Kanzerogenität sind wichtige Vorteile gegenüber herkömmlichen therapeutischen Verfahren. Entsprechende Zulassungen wurden daher mittlerweile sowohl in den USA als auch in Deutschland für die Indikationen aktinische Keratosen und Basalzellkarzinome erteilt. Der Einsatz der PDT auch bei entzündlichen Dermatosen wird derzeit im Rahmen klinischer Studien evaluiert.
Importance
Daylight photodynamic therapy using topical methyl 5-aminolevulinic acid (MAL) for actinic keratoses (AKs) is as effective as conventional photodynamic therapy but has the advantage of being almost pain free. Daylight photodynamic therapy, however, requires dry and warm weather conditions.Objective
To establish if topical MAL photodynamic therapy using a white light light-emitting diode (LED) lamp is as effective and well-tolerated as daylight photodynamic therapy for the treatment of AKs.Design, Setting, and Participants
Overall, 22 men with significant photodamage and a high number of AKs were enrolled in this prospective, randomized, single-blind study, employing a split-scalp design, comparing the effectiveness and adverse effects of daylight photodynamic therapy and artificial white light (AWL) LED photodynamic therapy for the treatment of AKs on the forehead and scalp. Organ transplant recipients were excluded. Patients were treated and evaluated at an academic tertiary referral dermatology center. Treatment lasted from April 2014 to July 2014 and follow-up visits occurred for 9 months posttreatment.Interventions
Two symmetrical treatment fields were defined and AKs counted, mapped, and photographed at baseline, 1, 3, 6, and 9 months. Patients had half of their scalp treated with daylight photodynamic therapy and the other half treated with AWL photodynamic therapy 1 week apart and randomly allocated. MAL was applied, and treatment commenced 30 minutes later and lasted 2 hours. Irradiance, illuminance, and light spectra measurements were performed. The integrated dose in J/cm2 was measured. The effective light dose, weighted to the absorption spectrum for protoporphyrin IX, was calculated.Main Outcomes and Measures
The primary end point was the reduction in total AK count per treatment field. Secondary end points included adverse effects and patient satisfaction.Results
We enrolled 22 men with a median age of 72 years (range, 47-85 years) at baseline, the total (median of AKs per field) were 469 (20.5) for the DPDT group and 496 (20.5) for the AWLPDT group (P = .34). The median number and percentage of reduction in AKs per field were 12 and 62.3% for DPDT and 14 and 67.7% for AWLPDT at 1 month (P = .21 and P = .13, respectively). There was no significant difference in the reduction percentage of AKs for either treatment at 1, 3, and 6 months. At 9 months, the median number and percentage of reduction in AKs per field was 9.0 and 48.4% for DPDT and 12.0 and 64.4% for AWLPDT (P = .13 and P = .05, respectively). Pain was reported by 14 patients with DPDT and 16 patients with AWLPDT (median maximum score [out of 100], 4 vs 6; P = .51). Moderate erythema was reported by 9 patients after DPDT and 14 patients after AWLPDT. On a scale of 0 (intolerable) to 10 (very tolerable) patients rated DPDT as 9.5 and AWLPDT as 9 (P = .37).Conclusions and Relevance
Photodynamic therapy using an AWL source was as effective and well-tolerated as daylight photodynamic therapy.Trial Registration
clinicaltrials.gov Identifier: NCT02520700
Leishmaniasis is a disease transmitted by protozoa of the genus Leishmania. Numerous species are responsible for the infection in humans, resulting in three clinical phenotypes. The therapeutic drug availability for treatment of this endemic disease is still limited and presents several problems. Photodynamic therapy (PDT) is presented as an alternative action for the treatment of cutaneous leishmaniasis (CL). Studies suggest that this therapy using porphyrins is relatively effective in the treatment of CL. However, data are still limited and PDT can not yet be recommended in clinical routine practice. Moreover, the mechanism of action of this promising therapy still needs to be investigated.
Photodynamic therapy (PDT) is currently used as a minimally invasive therapeutic modality for cancer. Whereas antitumor treatment regimens require lethal doses of photosensitizer and light, sublethal doses may have immunomodulatory effects, antibacterial action and/or regenerative properties. A growing body of evidence now indicates that non-lethal PDT doses can alleviate inflammation or treat established soft-tissue infections in various murine models of arthritis, experimental encephalomyelitis, inflammatory bowel disease and chronic skin ulcers. Furthermore, PDT is already used in clinical application and clinical trial for the treatment of psoriasis, chronic wounds and periodontitis in humans. Sublethal PDT should be regarded as a new viable option for the treatment of inflammatory conditions.
The objective of this study was to investigate the effect of power on low-level lasers used in photodynamic therapy (PDT) to treat chronic plaque psoriasis in a group of Sudanese patients.
Twenty-four patients with chronic plaque psoriasis were randomly selected to enter this study from a total of 100 patients who attended the Khartoum Dermatology Teaching Hospital between 2010 and 2011. The lasers used for PDT were three continuous wave diode lasers in the red portion of the electromagnetic spectrum (671–675 nm) with output powers of 16, 50 and 100 mW to activate the chemical photosensitizer (Levulan
This study showed that 62% of the patients treated with 100 mW achieved complete clearance compared with 25% for those treated with 50 mW and 0% for those treated with 16 mW.
The results showed that increasing the power of low-level laser in PDT increased the clearance of plaque psoriasis. PDT can be used as an alternative method for treatment of psoriasis.
Introduction:
Photodynamic therapy for psoriasis showed promise in the early 1990s with reports of plaque clearance following topical aminolevulinic acid - photodynamic therapy (ALA-PDT).
Methods:
In December 2013, we conducted a systematic search of the PubMed Medline database using the keywords "psoriasis" and "photodynamic therapy".
Results:
Numerous clinical studies have failed to demonstrate a consistent, efficacious response to topical ALA-PDT. Furthermore, severe pain and burning sensations were repeatedly reported, many cases being intolerable for patients.
Discussion:
The variability in clinical response and the painful side effects have made topical ALA-PDT an unsuitable treatment option for chronic plaque psoriasis. Nonetheless, early clinical studies of other modalities such as topical hypericin and methylene blue, as well as systemic ALA and verteporfin, have shown that these photosensitizers are efficacious and much better tolerated than topical ALA.
Conclusion:
With the current landscape of phototherapy dominated by psoralen combined with ultraviolet A (PUVA) and narrow-band ultraviolet B (NB-UVB), an alternative light therapy utilizing the visible spectrum is certainly promising and a worthwhile endeavor to pursue.
Topical photodynamic therapy (PDT) is a non-invasive therapeutic modality which is developing increasing use in dermatology. It is a well established treatment for pre-malignant and malignant skin tumours and over recent years there has also been encouraging evidence for its use in treating benign cutaneous disorders. We review the literature and clinical trials utilising topical PDT for non-cancerous skin conditions. Recalcitrant warts, acne vulgaris and psoriasis have so far been studied in most detail. At present, photosensitisers, light sources and treatment parameters of PDT vary in different clinical trials even for the same conditions. Optimum parameters for PDT need to be established and comparison randomised studies are required to clarify whether PDT for benign dermatoses is significantly superior to existing therapeutic modalities.
Photochemotherapy using oral psoralen and ultraviolet A radiation (PUVA) is a highly effective treatment for severe psoriasis but has carcinogenic potential. Photodynamic therapy (PDT) combining application of a photosensitizing porphyrin derivative and subsequent irradiation with red light may represent an alternative photochemotherapeutic modality with potentially a lower carcinogenic risk.In an attempt to limit potential side effects the concept of topical PDT has been persued for treating this inflammatory disease. In this context, the parameters determining susceptibility and selectivity of the targeted cell types as well as the biological effects induced in these cells could be defined. Following this pioneering work several photosensitizers were shown to exhibit good clinical efficacy in the topical PDT of psoriasis.Since the general feasibility of this approach is now well documented future studies will have to investigate the effectiveness of this modality in comparison to established regimen. Furthermore, the concept of PDT as antimicrobial regimen will have to be evaluated in the light of psoriasis being a disease triggered by bacterial superantigens.
Complications of cutaneous laser surgery can be understood by reviewing the evolution of laser technology over the past several
decades. Lasers initially were designed to operate in a continuous-wave (CW) mode, which produced a continuous beam of radiation
that subsequently was absorbed by a tissue chromophore. Although particular skin structures could be destroyed using these
early lasers, their use was limited because the energy emitted not only altered the target, but also conducted heat into adjacent
nonirradiated tissue. The nonselective thermal injury produced in adjacent tissue resulted in significant side effects and
complications; specifically, dyspigmentation, and scarring.1–3
Photodynamic therapy (PDT) is approved for the treatment of actinic keratoses, superficial and nodular basal cell carcinomas, and recently, Bowen's disease. In the last decade the advances experienced in the study of the photodynamic reaction have expanded the spectrum of application to other cutaneous diseases, neoplastic as well as inflammatory and infectious ones. The experience in psoriasis, acne, common warts and cutaneous T cell lymphoma starts to be broad and interesting, which permits to define its use in these entities. Photodynamic therapy is also been tested for a great variety of dermatoses with different photosensitizers and light sources with variable results. In this paper we review the treatment of Bowen's disease and other indications different from non melanoma skin cancer with PDT, providing our experience.
The new second edition of the Handbook of Psoriasis remains an easy-to-read but detailed text on a common skin disease which affects 2% of the world's population. The text is designed as a reference for both the specialist and the primary care physician and can be read cover-to-cover in a week. Each chapter stands alone as a reference to a specific topic but is clearly cross-referenced to offer a more detailed perspective. This new edition runs the full gamut from pathogenesis to clinical variants of psoriasis to individual treatments with emphasis on standard protocols. Each chapter has been carefully updated to reflect developments in the last five years and new chapters cover such topics as childhood psoriasis, psoriatic arthritis and biologic immunotherapy.
Light has been employed in the treatment of disease since antiquity. Many ancient civilizations utilized phototherapy, but it was not until early last century that this form of therapy reappeared. Following the scientific discoveries by early pioneers such as Finsen, Raab and Von Tappeiner, the combination of light and drug administration led to the emergence of photochemotherapy as a therapeutic tool. The isolation of porphyrins and the subsequent discovery of their tumor-localizing properties and phototoxic effects on tumor tissue led to the development of modern photodetection (PD) and photodynamic therapy (PDT). This review traces the origins and development of PD and PDT from antiquity to the present day.
In dermatology, photodynamic therapy (PDT) is meanwhile an established treatment modality for dermatooncologic conditions
like actinic keratoses (AK), Bowen’s disease, in situ squamous cell carcinoma, and superficial basal cell carcinoma (sBCC).
For many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare, and leishmaniasis,
a therapeutical benefit of PDT is evident, too. Esthetic indications like photoaging or sebaceous gland hyperplasia round
off the range of applications. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after
treatment. This chapter reviews the principal mechanism of action, the current developments in the field of photosensitizers
and light sources, practical aspects of topical PDT, and therapeutical applications in oncologic and nononcologic indications.
While still in its infancy, photodynamic therapy is becoming a prominent treatment option in a number of dermatological diseases,
such as psoriasis, lichen planus, lichen sclerosis, morphea/scleroderma, vitiligo, necrobiosis, lipoidica diabeticorum, sarcoidosis,
granuloma annulare, alopecia areata, and Darier’s disease. Given the breadth of clinical implications, it is clear that both
basic science and clinical studies are still needed to learn more about the mechanism of action, efficacy, and optimal treatment
regimens in many of these inflammatory disorders.
Während die Wirksamkeit der topischen photodynamischen Therapie (PDT) in der Behandlung von oberflächlichen, nicht pigmentierten
Hauttumoren inzwischen durch klinisch kontrollierte Studien hinreichend belegt ist, liegen nur wenige kontrollierte Studien
vor, die die Wirksamkeit der PDT auch in der Behandlung zahlreicher nichtonkologischer Hauterkrankungen zeigen. Im vorliegenden
Beitrag wird der Einsatz der PDT bei entzündlichen Dermatosen, Erkrankungen der Talgdrüsen und Haarfollikel, Infektionen der
Haut, sklerosierenden Hauterkrankungen und kosmetischen Indikationen vorgestellt und diskutiert.
While efficacy of topical photodynamic therapy (PDT) for the treatment of superficial non-melanoma skin cancer is already
well-proven by several controlled clinical trials, there are only a few controlled studies showing efficacy of PDT for non-oncologic
skin disorders. This report provides information on the use of PDT for inflammatory skin disorders, disorders of the pilosebaceous
unit, infections of the skin, sclerotic skin diseases and cosmetic indications.
A number of potentially therapeutical drugs, which are membrane impermeant, are captured and degraded in the lysosomes after cellular uptake, and are thereby prevented from executing their biological function. However, in the present thesis a technology is presented that makes it possible to overcome this substantial barrier for the cellular delivery of functional macromolecules. The technology, photochemical internalisation (PCI), is a unique procedure for light-induced release of several types of membrane impermeant molecules from endocytic vesicles to the cytosol of the target cells. The PCI technology can be utilised as a new efficient and site-specific method for drug delivery in the therapy of cancer and other diseases, and it can also be applied as research tool for macromolecule delivery both in vitro and in vivo.
Photodynamic therapy (PDT) involves the activation of a photosensitizing drug, which preferentially localizes to diseased skin, by irradiation with light to cause selective cytotoxic damage. Since its discovery in the early 20th century and the development of topical photosensitizers 2 decades ago, PDT is increasingly being used in dermatology for a wide range of neoplastic, inflammatory, and infectious cutaneous conditions. Topical 5-aminolevulinic acid and methyl aminolevulinic acid, the most commonly used agents in PDT, have received Food and Drug Administration approval for the treatment of actinic keratoses, and many second-generation photosensitizers are under investigation. Compared with conventional therapies, PDT has the advantage of being noninvasive and capable of field treatment. It is also associated with quicker recovery periods and excellent cosmetic results. Because of these benefits, PDT is being evaluated as a potential treatment option for many dermatologic conditions and has been shown to be effective for certain nonmelanoma skin cancers. Although research is still limited, PDT might also have a therapeutic benefit for cutaneous T-cell lymphoma, acne, psoriasis, leishmaniasis, and warts, among others. This article is a review of the clinical applications of PDT in dermatology and summarizes the current evidence in literature describing its efficacy, safety, and cosmetic outcome.
The combination of lesion ablation with excellence in cosmetic outcome has allowed photodynamic therapy (PDT) an ever increasing role in the treatment of diseases of the skin. As currently practiced, PDT employs a photosensitizing agent that when activated by light energy creates a photodynamic reaction that is cytotoxic and vasculotoxic. The relative simplicity of therapy with its ability to achieve high response rates has brought PDT to a worldwide audience not only for oncologic indications but far more commonly to non oncologic indications. This paper will review the mechanism of action for PDT and highlight the versatile clinical outcomes reported from the peer reviewed literature.
Photodynamic therapy (PDT) has been pioneered in dermatology at the beginning of the 20th century. Today, cutaneous treatments are the most common applications of PDT. Originating from cancer therapy, recent developments have widened the therapeutic spectrum, and now PDT indications range from inflammatory disorders to cosmetic applications. With several photosensitizers approved by regulatory agencies around the world, PDT continues demonstrating its inherent versatility. This review concentrates on aminolevulinic acid-based PDT regimens in dermatology. Recent research has helped to enhance the treatment efficacy of PDT and to further exploit its potential. Evolving strategies are being tested at present experimentally that will increase the power and diversity of cutaneous PDT. Ultimately these regimens will affect future development in clinical applications.
In recent years several review articles and books have been published on the use of porphyrin-based compounds in photodynamic therapy (PDT). This critical review is focused on (i) the basic concept of PDT, (ii) advantages of long-wavelength absorbing photosensitizers (PS), (iii) a brief discussion on recent advances in developing PDT agents, and (iv) the various synthetic strategies designed at the Roswell Park Cancer Institute, Buffalo, for developing highly effective long-wavelength PDT agents and their utility in constructing the conjugates with tumor-imaging and therapeutic potential (Theranostics). The clinical status of certain selected PDT agents is also summarized (205 references).
Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo-aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non-oncologic indications.
Infected wounds are a major cause of hospital-acquired infections and these are difficult to treat due to the emergence of antibiotic-resistant bacteria. This project is concerned with evaluating a novel antimicrobial approach involving the photosensitizer indocyanine green (ICG) which generates reactive oxygen species when irradiated with near-infrared (NIR) light which enables good tissue penetration. The photo-susceptibility of common wound-infecting organisms to ICG coupled with NIR-light was investigated. All species were
susceptible to killing. ICG at a concentration of 25 μg/mL enabled the killing of
the Gram-positive species (Staphylococcus aureus and Streptococcus
pyogenes), higher concentrations (100-200μg/mL) were necessary to achieve
substantial kills of the Gram-negative species (Pseudomonas aeruginosa and
Escherichia coli). Both high and low fluences were able to kill 99.999% of the
Gram-positive bacteria. High fluence irradiation was necessary to kill 99.99%
of the Gram-negative bacteria. The pulsed-mode of irradiation was as effective
as the continuous-mode for killing the Gram-positive species. Yet only the
continuous-mode of irradiation was able to kill P. aeruginosa. Biofilms of
Staph. aureus and P. aeruginosa were susceptible to disruption and killing by
ICG-photosensitization. A significant enhancement of lethal photosensitization
of Staph. aureus was achievable using gold-nanoparticles and antioxidants.
Significant kills (>99%) were achieved in the presence of serum and 100 μg/mL
ICG. A low oxygen concentration reduced the kills to 96.77% and 71.62% for
Staph. aureus and Strep. pyogenes respectively. Mechanistic studies
revealed that killing was mediated mainly by reactive-oxygen species.
In vivo studies in mice showed that ICG and continuous-NIR light could achieve
kills of 96%, 93% and 78-91% for P. aeruginosa, Strep. pyogenes and Staph.
aureus respectively.
The results of these in vitro and in vivo studies imply that ICG-PDT could be an
effective means of decreasing the microbial burden in wounds.
Photodynamic therapy (PDT) utilizes the destructive power of reactive oxygen species generated via visible light irradiation of a photosensitive dye accumulated in the cancerous tissue/cells, to bring about their obliteration. PDT activates multiple signalling pathways in cancer cells, which could give rise to all three cell death modalities (at least in vitro). Simultaneously, PDT is capable of eliciting various effects in the tumour microenvironment thereby affecting the tumour-associated/-infiltrating immune cells and by extension, leading to infiltration of various immune cells (e.g. neutrophils) into the treated site. PDT is also associated to the activation of different immune phenomena, e.g. acute-phase response, complement cascade and production of cytokines/chemokines. It has also come to light that, PDT is capable of activating 'anti-tumour adaptive immunity' in both pre-clinical as well as clinical settings. Although the ability of PDT to induce 'anti-cancer vaccine effect' is still debatable, yet it has been shown to be capable of inducing exposure/release of certain damage-associated molecular patterns (DAMPs) like HSP70. Therefore, it seems that PDT is unique among other approved therapeutic procedures in generating a microenvironment suitable for development of systemic anti-tumour immunity. Apart from this, recent times have seen the emergence of certain promising modalities based on PDT like-photoimmunotherapy and PDT-based cancer vaccines. This review mainly discusses the effects exerted by PDT on cancer cells, immune cells as well as tumour microenvironment in terms of anti-tumour immunity. The ability of PDT to expose/release DAMPs and the future perspectives of this paradigm have also been discussed.
Few studies have investigated subjective sensory skin symptoms in patients with psoriasis. The aim of this study was to investigate prevalence and characteristics of psoriasis-related skin pain and discomfort, and evaluate differences in demographic/clinical characteristics among patients with or without skin symptoms. A total of 139 patients was recruited for this exploratory, descriptive, cross-sectional study. Data were obtained through interviews and questionnaires. While 42.6% reported skin pain, 36.7% reported skin discomfort. Mean average symptom intensity score (0-10 numeric rating scale) was 4.4 for pain and 3.5 for discomfort. Unpleasant, surface, sensitive, itchy, and hot/burning were the most common symptom qualities. Sleep was the most severely affected function. No differences were found in demographic characteristics. However, larger proportions of patients with skin symptoms had more severe psoriasis (p < 0.05). In conclusion, pain and discomfort are more common and more severe in patients with psoriasis than previously estimated.
Photodynamic therapy (PDT) consists of the combination of photosensitizers absorbing light mainly in the red spectral region and irradiation with light of corresponding wavelengths. We analysed its effects on the cytokine secretion (IL-1 beta, TNF alpha, IL-6) of freshly isolated peripheral mononuclear cells from six patients with chronic plaque-stage psoriasis in comparison with PUVA. PUVA treatment resulted in a decreased production of all three cytokines, but most pronounced in the case of IL-6. PDT caused a similar change in the cytokine pattern, but its effectiveness was lower. In vivo fluorescence recordings were performed on psoriatic plaque lesions after topical application of the photosensitizer Photosan-3. Under irradiation, progressive photobleaching was noted with increasing radiation dosage. This is the first reported study of photochemical reactions using on-line fluorescence recordings during PDT of psoriatic lesions in vivo. Our results demonstrate the capacity of PDT to cause immunomodulatory effects similar to PUVA, thus indicating its potential application to the treatment of this common disease.
Fourier transform multipixel spectroscopy was applied to subcellular localization of endogenous protoporphyrin (endo-PP) in single living B16 melanoma cells during photosensitization. Continuous fluorescence spectra for each pixel were recorded using a Sagnac interferometer coupled to a charge-coupled device camera. Multiple frames of data were acquired for each pixel composing the image, then they were stored as interferometric data and resolved as spectra for every pixel (10(3)-4 x 10(3) point pixels in a single cell). The net result was the intensity I (x, y, gamma), for each pixel of the image (x,y), at any wave-length (gamma). The present study demonstrates the application of Fourier transformed multipixel spectroscopy for spectral imaging of melanoma cells incubated with 5-aminolevulinic acid (ALA). The fluorescence image of ALA-treated cells revealed endo-PP all over the cytosol with a vesicular distribution, which represent mitochondria and endoplasmic reticulum compartments. Two main spectral fluorescence peaks were demonstrated at 630 and 670 nm, of monomeric and aggregated protoporphyrin, with intensities that differed from one subcellular site to another. Photoirradiation of the cells induced point-specific subcellular fluorescence spectrum changes and demonstrated photoproduct formation. Spectral-image reconstruction revealed the subcellular distribution of porphyrin species in single photosensitized cells. Multipixel spectroscopy of exogenous protoporphyrin revealed an endosomal-lysosomal compartment in aggregated states, whereas monomeric porphyrin species were localized mainly on the outer membrane. Photo-products could be visualized at sites of formation in subcellular compartments.
5-Aminolaevulinic acid (ALA) is a precursor of protoporphyrin IX (Pp IX) in the biosynthetic pathway for haem. Certain types of cells have a large capacity to synthesize Pp IX when exposed to an adequate concentration of exogenous ALA. Since the conversion of Pp IX into haem is relatively slow, such cells tend to accumulate photosensitizing concentrations of Pp IX. Pp IX photosensitization can be induced in cells of the epidermis and its appendages, but not in the dermis. Moreover, since ALA in aqueous solution passes readily through abnormal keratin, but not through normal keratin, the topical application of ALA in aqueous solution to actinic keratoses or superficial basal cell or squamous cell carcinomas induces Pp IX photosensitization that is restricted primarily to the abnormal epithelium. Subsequent exposure to photoactivating light selectively destroys such lesions. In our ongoing clinical trial of ALA-induced Pp IX photodynamic therapy, the response rate for basal cell carcinomas following a single treatment has been 90% complete response and 7.5% partial response for the first 80 lesions treated. The cosmetic results have been excellent, and patient acceptance has been very good.
We have used ultra-low light level fluorescence microscopy to examine the suggestion that the relatively poor response of human basal cell carcinomas (BCC) to topical 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) arises from limited drug penetration into the lesion. The distribution of ALA-induced protoporphyrin IX (PpIX) in human BCC and Bowen's disease was examined and, in almost all cases, was found to be most intense in those regions of tumor immediately adjacent to the dermis. This distribution was independent of tumor type, and did not appear to be affected by tumor depth in the skin. It is suggested that ALA penetration may not limit the efficacy of ALA-PDT in the treatment of BCC. Failure of superficial ALA-based PDT in basal cell carcinoma may, instead, be related to the histological structure of this type of lesion.
Photodyamic therapy (PDT) is considered a promising treatment modality for a variety of solid tumours. Recently, beneficial effects of PDT in psoriasis have been described. In this study the effectiveness of topical PDT in psoriasis using different sensitizers was compared with treatment with dithranol. Three patients with chronic plaque-stage psoriasis were treated twice a week with PDT using either methylene blue (MB) or 5-aminolaevulinic acid (ALA) as photosensitizers. An ointment containing 10% MB and another containing 10% ALA were applied topically to defined plaque lesions 5 h before irradiation. Light in the wavelength range 600 - 700 nm emitted by a 1200 W lamp (prototype Waldman 1200, Waldmann, Germany) was used for treatment (dose 5 J/cm2, power density 70 mW/cm2). The responses of the PDT-treated lesions using MB or ALA were comparable to those of dithranol-treated lesions in all patients. In all areas treated with PDT with ALA a burning sensation was noted, whereas no burning sensation occurred with PDT with MB. This study illustrates the therapeutic effect of PDT in psoriasis. The use of MB as a photosensitizer seemed to minimize the burning sensation, the main side-effect reported so far in topical PDT. (/ Dermatol Treat (1997) 8: 17–19)
Photodynamic therapy (PDT) with topical application of 5-aminolaevulinic acid (ALA, 20% w/w) was used to treat superficial basal cell carcinoma (BCC, 16 patients), Morbus Bowen (one patient), basal cell naevus syndrome (BCNS, three patients), actinic keratosis (AK, two patients), chronic inflammation (CI, one patient), and metastasized BCC (one patient). The interval between ALA application and illumination was 3–6 h. The incident light dose was 50–100 J cm–2, mostly 75 J cm–2, at 633 nm wavelength. This was based on the fluorescence excitation spectrum, measured on the skin of human volunteers. In a few cases, 514.5 nm light was used. A complete response (CR) rate of 79% (median follow-up 13 months) was obtained with 42 BCC lesions. The treatment of five areas with AK, two areas with CI and one area with M. Bowen yielded three CR for AK and five partial remissions (PR). Photodynamic therapy of metastasized BCC, after either topical or oral ALA, was not successful. Treatment of BCNS was satisfactory with 100% CR in one patient (22 lesions), PR in a second patient (20 lesions), and good palliation in a third patient (>250 lesions). The treatment was well tolerated, although the illumination had to be interrupted occasionally due to pain. Healing usually occurred in 2 weeks. Cosmetic results were good to excellent. 5-Aminolaevulinic acid application over 16–19 h and repeated treatments made it possible to obtain CR of non-superficial lesions. The selective tumour fluorescence was then lost, however, due to fluorescence of normal skin, but the cosmetic outcome did not deteriorate. 5-Aminolaevulinic acid PDT may be a good alternative outpatient treatment, especially in elderly patients and for large treatment areas. The excellent cosmetic outcome warrants further study in younger patients. More work is necessary to establish optimal ALA-treatment schemes.
The tissue photosensitizer protoporphyrin IX (PpIX) is an immediate precursor of heme in the biosynthetic pathway for heme. In certain types of cells and tissues, the rate of synthesis of PpIX is determined by the rate of synthesis of 5-aminolevulinic acid (ALA), which in turn is regulated via a feedback control mechanism governed by the concentration of free heme. The presence of exogenous ALA bypasses the feedback control, and thus may induce the intracellular accumulation of photosensitizing concentrations of PpIX. However, this occurs only in certain types of cells and tissues. The resulting tissue-specific photosensitization provides a basis for using ALA-induced PpIX for photodynamic therapy. The topical application of ALA to certain malignant and non-malignant lesions of the skin can induce a clinically useful degree of lesion-specific photosensitization. Superficial basal cell carcinomas showed a complete response rate of approximately 79% following a single exposure to light. Recent preclinical studies in experimental animals and human volunteers indicate that ALA can induce a localized tissue-specific photosensitization if administered by intradermal injection. A generalized but still quite tissue-specific photosensitization may be induced if ALA is administered by either subcutaneous or intraperitoneal injection or by mouth. This opens the possibility of using ALA-induced PpIX to treat tumors that are too thick or that lie too deep to be accessible to either topical or locally injected ALA.
5-Aminolaevulinic acid (ALA) is a precursor of protoporphyrin IX (Pp IX) in the biosynthetic pathway for haem. Certain types of cells have a large capacity to synthesize Pp IX when exposed to an adequate concentration of exogenous ALA. Since the conversion of Pp IX into haem is relatively slow, such cells tend to accumulate photosensitizing concentrations of Pp IX. Pp IX photosensitization can be induced in cells of the epidermis and its appendages, but not in the dermis. Moreover, since ALA in aqueous solution passes readily through abnormal keratin, but not through normal keratin, the topical application of ALA in aqueous solution to actinic keratoses or superficial basal cell or squamous cell carcinomas induces Pp IX photosensitization that is restricted primarily to the abnormal epithelium. Subsequent exposure to photoactivating light selectively destroys such lesions. In our ongoing clinical trial of ALA-induced Pp IX photodynamic therapy, the response rate for basal cell carcinomas following a single treatment has been 90% complete response and 7.5% partial response for the first 80 lesions treated. The cosmetic results have been excellent, and patient acceptance has been very good.
The separation and quantitation of plasma free acid porphyrins by high-pressure liquid chromatography and fluorescence is described. Porphyrins were extracted from plasma in a simple manner with a recovery >90%. They were separated by high-pressure liquid chromatography on a silica gel (10 μm) column, using a gradient of acetone:dilute acetic acid. Resolution of seven free acid porphyrin standards including coproporphyrins I and III, but not uroporphyrins I and III, was achieved in 12 min at picomolar concentrations. Plasma of patients with erythropoietic protoporphyria displayed protoporphyrin. Uroporphyrin was the only porphyrin found in plasma of eight patients with porphyria cutanea tarda. Normal plasma contained small amounts of uroporphyrin and/or traces of protoporphyrin.
Temperature monitoring during photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) cream application was performed on 22 patients with solar keratoses (SK) and basal cell carcinoma (BCC). The lesions were located on the forehead, nose, ear and cheek. Temperature measurements during photoirradiation, with a power density of 100 mW/cm2 from an incoherent light source (light delivery system for PDT), were carried out by noncontact (infrared thermal imaging radiometer) and contact (thermocouple) methods. Thermal imaging analysis revealed nonuniform temperature distribution in the irradiated areas. The temperature gradually increased from the peripheral to the central zone of the area. The results showed that photoirradiation induced heating of the skin tumors to 39.5-42.5 degrees C during the PDT procedure. The temperature of normal skin areas disposed symmetrically to the lesions on the contralateral side at the same conditions of irradiation (without prior ALA application) was about 42-43.5 degrees C. The surface temperature differences (delta T) between the normal and tumor tissues after 10 min of irradiation were 3.3 +/- 0.5 degrees C in the forehead areas, 2.5 +/- 0.4 degrees C in the nose areas and 0.8 +/- 0.3 degrees C in the ear areas.
Eighty basal cell carcinomas (BCCs) in 21 patients, 10 lesions of Bowen's disease in three patients, and four lesions of cutaneous T-cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor delta-amino levulinic acid (ALA). The diagnoses were confirmed histologically prior to treatment. Fifty-five of the BCCs were superficial lesions, and 25 were nodular. Of the 80 BCCs, 39 (49%) were located on the trunk, 36 (45%) on the head and neck region, four (15%) on the leg and one on the arm. The two principal locations of the 10 Bowen's disease lesions were the leg (50%) and the trunk (40%). The T-cell lymphoma lesions were located on the shoulder and on the arm. A water-in-oil based cream containing 20% ALA was applied to the lesions, with a margin of about 10-20 mm beyond the visible tumour border, 4-6 h before the laser procedure. During this period of time the highly fluorescent and photodynamically active substance protoporphyrin IX (Pp IX) is synthesized via the haem cycle. Laser-induced fluorescence (LIF) was used for real-time monitoring of the Pp IX distribution in the tumour and in the normal surrounding skin, before and after treatment in all patients. Before laser treatment the Pp IX distribution demonstrated by LIF showed a demarcation between tumour and normal skin of about 15:1 for BCC and Bowen's disease, and 5:1 for T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)
The success reported for the treatment of superficial skin carcinomas by photodynamic therapy with topical application of the photosensitizer precursor 5-aminolevulinic acid has therapeutic implications for the treatment of other skin disorders. This paper describes the accumulation of the photosensitizing agent protoporphyrin IX in areas of plaque psoriasis by monitoring of the fluorescence emission induced by low-intensity laser excitation at 488 nm. We present results from 15 patients with a total of 42 plaques and show that the characteristic fluorescence emission of protoporphyrin IX increases in intensity within the 6-h period following application of 5-ami-nolevulinic acid, suggesting that there is a potential for superficial photodynamic therapy. The rate of increase and maximum intensity of fluorescence emission was not directly related to the applied quantity of the precursor. The variability of the fluorescence intensity was as great between plaques at different sites on the same patient as between different patients. Also, the effect of plaque occlusion following application appeared insignificant. Although there was only limited enhancement of emission from areas of skin surrounding the plaque, a significant buildup of sensitizer was detected after several days in some areas of psoriasis that received no application.
Large patches of Bowen's disease (intraepidermal carcinoma in situ) can be difficult to treat by conventional methods. Photodynamic therapy (PDT) uses the combination of a photosensitizer, which preferentially accumulates in malignant cells, and photoactivation by visible light to kill the malignant cells. 5-aminolaevulinic acid (ALA) PDT uses excess exogenous ALA, which produces, via the haem synthesis pathway, a build up of the photosensitizer protoporphyrin IX. We describe the use of topical ALA PDT to treat three patients with three especially large patches of Bowen's disease. Following two treatments all three lesions achieved a complete clinical and histological response with a good cosmetic result. ALA PDT is a simple, effective and well tolerated treatment for large patches of Bowen's disease.
We have investigated the clinical response of 22 patients with plaque psoriasis to photodynamic therapy using topical application of 5-aminolaevulinic acid followed by a single exposure to broad-band visible radiation. Light doses in the range 2-16 J/cm2 delivered at dose of 10-40 mW/ cm2 resulted in a variable clinical response. Seven (35%) patients showed clearing of psoriasis at some treated sites. The intensity of protoporphyrin IX fluorescence was recorded before, during and after treatment. Pre-illumination fluorescence intensity varied considerably between sites on the same patient and between patients. Protoporphyrin IX fluorescence recovered and persisted after treatment for up to 14 days and became higher than preillumination levels at 25% of sites. The rate of protoporphyrin IX photo-oxidation during treatment was proportional to both initial fluorescence intensity and incident light dose rate and was almost complete after 16 J/cm2. We have defined the photodynamic dose as the product of time-dependent protoporphyrin IX concentration and light dose and demonstrated that only in those patients who showed clearance of psoriasis was there a relationship between photodynamic dose and clinical response. Discomfort ranged from stinging through to burning, was significant in some patients and tended to be more severe with increasing photodynamic dose but was not predictable. Efficacy may improve by achieving consistent protoporphyrin IX levels or by using multiple treatments.
The photobleaching of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was investigated during superficial photodynamic therapy (PDT) in normal skin of the SKH HR1 hairless mouse. The effects of light dose and fluence rate on the dynamics and magnitude of photobleaching and on the corresponding PDT-induced damage were examined. The results show that the PDT damage cannot be predicted by the total light dose. Photobleaching was monitored over a wide range of initial PpIX fluorescence intensities. The rate of PpIX photobleaching is not a simple function of fluence rate but is dependent on the initial concentration of sensitizer. Also, at high fluence rates (50-150 mW/cm2, 514 nm) oxygen depletion is shown to have a significant effect. The rate of photobleaching with respect to light dose and the corresponding PDT damage both increase with decreasing fluence rate. We therefore suggest that the definition of a bleaching dose as the light dose that causes a 1/e reduction in fluorescence signal is insufficient to describe the dynamics of photobleaching and PDT-induced damage. We have detected the formation of PpIX photoproducts during the initial period of irradiation that were themselves subsequently photobleached. In the absence of oxygen, PpIX and its photoproducts are not photobleached. We present a method of calculating a therapeutic dose delivered during superficial PDT that demonstrates a strong correlation with PDT damage.
Large patches of Bowen's disease treated by topical aminolaevulinic acid photodynamic therapy Endogenous protoporphyrin IX, a clinically useful photosensitiser for photodynamic therapy
- Gi Stables
- Mr Stringer
- Dj Robinson
- Dv Ash
- Kennedy Jc
- Pottier
Stables GI, Stringer MR, Robinson DJ, Ash DV. Large patches of Bowen's disease treated by topical aminolaevulinic acid photodynamic therapy. Br J Dermatol 1997; 136: 957 ± 960. 6. Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitiser for photodynamic therapy. J Photochem Photobiol B: Biol 1992; 11: 275 ± 292.
Detection of auto¯uorescence due to protoporphyrin IX in the stratum corneum of psoriasis plaques
- R Bissonnette
- H Zeng
- Di Mclean
- Schreiber
Bissonnette R, Zeng H, McLean DI, Schreiber WE. Detection of auto¯uorescence due to protoporphyrin IX in the stratum corneum of psoriasis plaques. Abstracts of the 25th Annual Meeting of the American Society for Photobiology 1997; 49S.